Organ Responses, Survival, and Safety of Belumosudil in Chronic Graft-Versus-Host Disease: A Systematic Review and Meta-Analysis.

Chronic graft-versus-host disease (cGVHD) is a complex, immune-mediated, multisystem disease with a high symptom burden. While treatment with systemic corticosteroids is first-line, approximately 70% of patients require additional treatments because of either inadequate efficacy or steroid toxicity, highlighting the need for effective steroid-sparing therapies. Belumosudil, an oral ROCK2 inhibitor, has been studied in trials and real-world cohorts with varying results. We set out to systematically evaluate and meta-analyze the efficacy and safety of belumosudil in cGVHD. We systematically searched PubMed, Scopus, Web of Science, and Cochrane Library databases for relevant studies published up until August 2025. Eligibility criteria were predefined to identify relevant studies assessing belumosudil for cGVHD. Quality assessment of included studies was assessed using the MINORS tool. Meta-analysis was conducted using Comprehensive Meta-Analysis (v.3), adopting an inverse variance random effect model. Systematic literature search yielded inclusion of eleven studies (total participants = 477 patients). At 12 months, the pooled overall response rate (ORR) was 73% (95% CI 64-81) and 58% of patients showed a reduction in corticosteroid use with 95% CI (46%-70%), with improvement in patient-reported quality of life assessed by the Lee Symptom Scale. In a meta-regression analysis, higher baseline cGVHD severity independently predicted corticosteroid tapering success (β = 0.027; OR = 1.03; p = 0.031). Overall survival was 87% (95% CI 82-91) at 12 months and 85% (95% CI 79-90) at 24 months; failure-free survival at 12 months was 65% (95% CI 52-75). Regarding safety of belumosudil, any-grade adverse events occurred in 98% (95% CI 95-99), serious adverse events in 38.9% (95% CI 32.6-45.6); common events were diarrhea 22.1%, headache 22.3%, and fatigue 20.5%. Belumosudil exhibits significant clinical efficacy in cGVHD refractory or dependent on steroids, evidenced by a high objective response rate at 12 months, substantial steroid-sparing benefits, durable survival, and amelioration of disease-associated symptoms.